The Journal of Neuroscience, April 1, 2003, 23(7):2779
Visualizing Changes in Circuit Activity Resulting from
Denervation and Reinnervation Using Immediate Early Gene Expression
Meredith D.
Temple1,
Paul F.
Worley2, and
Oswald
Steward1
1 Reeve-Irvine Research Center, Departments of Anatomy
and Neurobiology, and Neurobiology and Behavior, University of
California at Irvine, Irvine, California 92697, and
2 Departments of Neuroscience and Neurology, Johns Hopkins
University, Baltimore, Maryland 21205
We describe a novel strategy to evaluate circuit function after
brain injury that takes advantage of experience-dependent immediate
early gene (IEG) expression. When normal rats undergo training or are
exposed to a novel environment, there is a strong induction of IEG
expression in forebrain regions, including the hippocampus. This gene
induction identifies the neurons that are engaged during the
experience. Here, we demonstrate that experience-dependent IEG
induction is diminished after brain injury in young adult rats
(120-200 gm), specifically after unilateral lesions of the entorhinal
cortex (EC), and then recovers with a time course consistent with
reinnervation. In situ hybridization techniques were
used to assess the expression of the activity-regulated
cytoskeleton-associated protein Arc at various times after the
lesion (4, 8, 12, 16, or 30 d). One group of rats was allowed to
explore a complex novel environment for 1 hr; control operated animals
remained in their home cage. In unoperated animals, exposure to the
novel environment induced Arc mRNA levels in most pyramidal neurons in
CA1, in many pyramidal neurons in CA3, and in a small number of dentate
granule cells. This characteristic pattern of induction was absent at early time points after unilateral EC lesions (4 and 8 d) but recovered progressively at later time points. The recovery of Arc
expression occurred with approximately the same time course as the
reinnervation of the dentate gyrus as a result of postlesion sprouting.
These results document a novel approach for quantitatively assessing
activity-regulated gene expression in polysynaptic circuits after trauma.
Key words:
immediate early gene; reinnervation; denervation; recovery of function; sprouting; entorhinal cortex; hippocampus; fimbria-fornix; diaschisis; rat; Arc
Copyright © 2003 Society for Neuroscience 0270-6474/03/2372779-10$05.00/0
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